A fluidized bed is created when a gas or liquid is passed upwardly through a bed of solid particles with sufficient velocity wherein the drag forces of the gas or liquid counterbalance the gravitational forces on the particle and cause the bed to expand. A fluidized bed consists of particles that are completely submerged and levitated in the fluidizing fluid. In contrast, in a "packed" bed, the particles are fixed in space and have no translational freedom, due to their permanent contact with particles (or walls) surrounding them.
Ronald E. Rosensweig was the first to investigate the possibility of forming a "stabilized" fluidized bed by utilizing magnetizable particles and placing the system in a magnetic field. See R. Rosensweig, Fluidization: Hydrodynamic Stabilization With a Magnetic Field, 204 Science, pp. 57-60 (1979). Rosensweig's research concentrated on gas/solid systems. In gas/solid fluidized beds--used in heterogeneous chemical reactions such as hydrocarbon cracking--bubble formation greatly reduces the effectiveness of the process. Rosensweig discovered that by utilizing magnetizable particles in a radially uniform magnetic field, it was possible to create a "stabilized" fluid bed. Rosensweig, and others, have reported that the stabilization effect is more easily accomplished when the magnetic field runs parallel to the path of fluid flow.
A discussion of magnetically stabilized fluidized beds ("MSFB") in liquid/solid systems is found in J. H. Siegell, Liquid-Fluidized Magnetically Stabilized Beds, 52 Powder Technology, pp. 139-48 (1987). The effects of the magnetic stabilization are not as dramatic as those seen in the gas/solid systems, but nonetheless are quite significant. Siegell characterized four regimes in upwardly flowing solid particle beds: packed, stable, random motion and boiling.
In the absence of a radially-uniform magnetic field, a system utilizing the upward flow of fluid through a particle bed goes through three regimes as the velocity of fluid flow is increased. The "packed" regime is the same as in the presence of the magnetic field. At the point of "incipient fluidization"--where the velocity of the fluid creates drag forces that exactly counterbalance the gravitational effects on the particles--the random motion regime begins. With increased fluid flow velocity, the boiling regime can be seen.
The point of incipient fluidization is also the transition between the packed and stable regimes in MSFB. This point is not affected by the strength of the magnetic field applied. One can reach the stable regime either by first applying the magnetic field and then increasing the flow above the point of incipient fluidization, or by applying a magnetic field to the bed in the random motion regime already above the point of incipient fluidization.
When in the stable regime, the pressure drop in the bed remains constant with increased flow rate, the void volume of the bed increases, yet there is restricted motion of the particles due to the existence of the magnetic field. In the stable regime the bed of particles is clearly fluidized (expanded and flowable), yet it lacks the random motion traditionally associated with fluidized beds.
The effect of the magnetic field can be viewed roughly as creating a magnetic dipole in each particle, which causes it to become "sticky" in a direction parallel to the magnetic field lines. This produces what amounts to the formation of chains of beads parallel to the axis of the bed. For a detailed mathematical/theoretical investigation of the mechanism for MSFB, see Rosensweig et al., Continuum Modes of Discrete Systems4, O. Brulin and R. K. T. Hsieh, eds., North Holland Publishers, Amsterdam, 137-143 (1981).
References that describe the use of MSFB in conjunction with either adsorption/desorption or chromatographic separations are limited. Of course, the use of magnetizable particles in biochemical systems is relatively common. The references that disclose the use of MSFB have been restricted to affinity interactions.
Work described by Burns and Graves is directed towards a system using counter-current liquid/solid phase continuous affinity chromatography. See M. Burns and D. Graves, Continuous Affinity Chromatography Using a Magnetically Stabilized Fluidized Bed, 1 Biotechnol. Prog., pp. 95-103 (1985), M. Burns and D. Graves, Application of Magnetically Stabilized Fluidized Beds to Bioseparations, 6 Reactive Polymers, pp. 45-50 (1987); and M. Burns and D. Graves, Structural Studies of a Liquid-Fluidized Magnetically Stabilized Bed, 67 Chem. Eng. Comm., pp. 315-330 (1988). Rather than utilizing a stationary column of magnetizable particles, Burns and Graves anticipate using a system where the particles flow downwardly as the solution flows upwardly.
A paper by Lochmuller and Wigman also deals with the use of MSFB and affinity interactions. C. H. Lochmuller and L. S. Wigman, Affinity Separations in Magnetically Stabilized Fluidized Beds, 22 Separation Science and Technology, pp. 2111-2125 (1987). Although utilizing a magnetizable affinity particle, the particle used is of the non-porous, pellicular type. In such a system, only surface adsorption is possible.
Although affinity interactions can yield superb selectivity, it is an expensive technique for separating proteins. The great selectivity seen means that only single-protein specific particles can be prepared.
As mentioned above, the use of magnetizable particles is not unknown in biotechnology. The separation of proteins from mixtures by adsorption unto magnetizable particles--either hydrophobic, affinity or ion-exchange types--is often performed in batch preparations. The particle beads can be held in the bottom of a container with a magnet while excess solutions and wastes can be decanted out of the container. At the same time, the adsorbed proteins will remain with the particles. However, as is generally the case, for scale-up purposes it is usually more efficient to perform separations of this type on a column in a more or less continuous process.
An example of a procedure used to prepare a Sepharose based magnetizable particle using a ferrofluid is described in M. Mosbach and L. Andersson, Magnetic Ferrofluids for Preparation of Magnetic Polymers and Their Application in Affinity Chromatography, 270 Nature, pp. 259-261 (1977).
Combining the batch type adsorption processes into a column would provide certain advantages. However, by taking advantage of the MSFB, protein isolation performance can be greatly enhanced. Unlike many other separation schemes, fluidized beds are quite conducive to scaling up. No examples of a magnetizable, porous and stationary particle bed for ion-exchange adsorption/desorption or chromatography in an MSFB has been disclosed in the literature.